Flück Martin, Viecelli Claudio, Bapst Andreas M, Kasper Stephanie, Valdivieso Paola, Franchi Martino V, Ruoss Severin, Lüthi Jean-Marc, Bühler Martin, Claassen Helgard, Hoppeler Hans, Gerber Christian
Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Department of Orthopedic Surgery, Inselspital Bern, Bern, Switzerland.
Front Physiol. 2018 Sep 25;9:1343. doi: 10.3389/fphys.2018.01343. eCollection 2018.
We investigated molecular and cellular parameters which set metabolic and mechanical functioning of knee extensor muscles in the operated and contralateral control leg of 9 patients with a chronically insufficient anterior cruciate ligament (ACL; 26.6 ± 8.3 years, 8 males, 1 female) after open reconstructive surgery (week 0), after ambulant physiotherapy under cast immobilization (week 9), succeeding rehabilitation training (up to week 26), and subsequent voluntary physical activity (week 260). Clinical indices of knee function in the operated leg were improved at 52 weeks and remained at a comparable level at week 260. CSA of the quadriceps (-18%), MCSA of muscle fibers (-24%), and capillary-to-fiber ratio (-24%) in from the ACL insufficient leg were lower at week 0 than reference values in the contralateral leg at week 260. Slow type fiber percentage (-35%) and mitochondrial volume density (-39%) were reduced in from the operated leg at weeks 9 and 26. Composition alterations in the operated leg exceeded those in the contralateral leg and, with the exception of the volume density of subsarcolemmal mitochondria, returned to the reference levels at week 260. Leg-specific deterioration of metabolic characteristics in the from the operated leg was reflected by the down-regulation of mitochondrial respiration complex I-III markers (-41-57%) at week 9. After rehabilitation training at week 26, the specific Y397 phosphorylation of focal adhesion kinase (FAK), which is a proxy for mechano-regulation, was elevated by 71% in the operated leg but not in the contralateral leg, which had performed strengthening type exercise during ambulant physiotherapy. Total FAK protein and Y397 phosphorylation levels were lowered in both legs at week 26 resulting in positive correlations with mitochondrial volume densities and mitochondrial protein levels. The findings emphasize that a loss of mechanical and metabolic characteristics in knee extensor muscle remains detectable years after untreated ACL rupture, which may be aggravated in the post-operative phase by the deterioration of slow-oxidative characteristics after reconstruction due to insufficient load-bearing muscle activity. The reestablishment of muscle composition subsequent to years of voluntary physical activity reinforces that slow-to-fast fiber transformation is reversible in humans.
我们研究了9例慢性前交叉韧带（ACL）功能不全患者（年龄26.6±8.3岁，8例男性，1例女性）在开放重建手术后（第0周）、石膏固定下的门诊物理治疗后（第9周）、后续康复训练（至第26周）以及随后的自主体育活动（第260周）时，决定患侧和对侧膝关节伸肌代谢和机械功能的分子和细胞参数。患侧膝关节功能的临床指标在第52周时有所改善，并在第260周时保持在相当水平。ACL功能不全侧股四头肌的横截面积（-18%）、肌纤维的平均横截面积（-24%）和毛细血管与纤维的比例（-24%）在第0周时低于对侧在第260周时的参考值。在第9周和第26周时，患侧慢肌纤维百分比（-35%）和线粒体体积密度（-39%）降低。患侧的成分改变超过对侧，除肌膜下线粒体的体积密度外，在第260周时恢复到参考水平。患侧腿部代谢特征的特异性恶化在第9周时表现为线粒体呼吸复合体I-III标志物下调（-41 - 57%）。在第26周的康复训练后，作为机械调节指标的粘着斑激酶（FAK）的特异性Y397磷酸化在患侧升高了71%，而在门诊物理治疗期间进行强化运动的对侧则未升高。在第26周时，双侧的总FAK蛋白和Y397磷酸化水平均降低，导致与线粒体体积密度和线粒体蛋白水平呈正相关。这些发现强调，未经治疗的ACL断裂多年后，膝关节伸肌的机械和代谢特征丧失仍可检测到，重建后由于承重肌肉活动不足导致慢氧化特征恶化，这在术后阶段可能会加剧。多年自主体育活动后肌肉成分的重建进一步证明，人类慢肌纤维向快肌纤维的转变是可逆的。
